N-(2-cyanoethyl)-2-pyrrolidone-5-carboxylic acid and methods for its preparation



i atented Aug. 8, 1950 N-(I2'JCYANOETHYM 2..-rRRoLmoNE-.5-

CARBOXYLIC ACID annmc'rnons FOR ITS PREPARATION .LeonardL. MoKinneyp,Eugene H. Uhing, and John :0. CYqwan, Peoria, 111., assignors to thenitedStatesfif America :as: represented by the =8ecretary ofngi'iculture1 No Drawing. Application November 22, 1349,

.Serial No. 128,904

(Granted under the act pfMa-rch *3, 1883, as amendedpril 30, 1928; '3700J- G. 757) Thiszapplicationis made under. the; acto f March .3, .1883,ras arnended,by .thaact of Aprildq 1928, and .the invention hereindescribed: if paffl nfied in anyqcountry, may lbe manufactured and ,usedby oryforlthe Government of ithe .United States of America forgovernmental purposes throughout the.world-withoutxthe payment to us ofany royalty tthereon.

This inventionrelatesto'a novel chemical compound N- (Z-cyanoethyl)-2-pyrrolidone-5-carboxylic acid, which-may a-ismbedesignated N-(2-cyanoethyl) -glutiminic acid, or more conveniently cyanoethyl-glutiminicacid. This invention also relates to novel methods for its preparation.The compound has the following formula:

It is a white crystalline compound, soluble in water and organicsolvents, and is useful as an intermediate in the preparation ofsynthetic resins, artificial fibers, plastics, plasticizers,pharmaceuticals and other products.

The compounds may be made by reactions which may be shown schematicallyas follows:

NH: NH-CHz- OHz-ON JH-COONE H2O H-COONB.

+CH2=CH-CN H2 5 to 50 C. H:

Hz-COON8 CHrCOONa (I) (II) (mineral acid) (1;

2 H01 lE[-C O OH (mineral acid salt) 2Na0l H2- 0 O O E (III)NC-CHr-CH2N-CH-C O OH Acetone O=C Hz (+2Na0l) +1120 Reflux er e warnd-ta t: at $0 1 tem a low. It may b ifiect rr wi l qu n tat l i yf y eee t mnoim m a ts wi h dra :m y berat d dir ct itv rp sw na' c ve tmaqumsuhz iex m la acetoneor water.

In the process as-shown above, compounds II and III need not be";isolated, The mineral acid 1 11?ad s wi hwmn t d I I-n ded r s mrated,for whenwater*is removed from the mixture an'd theres' ue is renuxedwith acetone,

"compound-"IV is-formed and goes into solution. The salt remainsinsoluble and may be removed by filtration. Compound IV may then berecovered in crystalline form by methods known to those skilled in theart.

The starting glutamic acid may be in any of its optically active formsor racemic mixture and, moreover, may be comprised in a crude mixture ofalpha amino acids, such as is obtained from protein hydrolysates. Uponreacting such mixtures of amino acids with acrylonitrile,monocyanoethyl-glutamic acid may be readily converted tocyanoethyhglutiminic acid whereupon it can be readily isolated from thereaction mixture because of its solubility characteristics.

The following examples are illustrative of the methods of carrying outthe invention:

EXAMPLE 1 Two moles (294.26 g.) of l-glutamic acid was suspended in 250ml. of water, and 200 m1. of water containing 4 moles (160.0 g.) ofsodium hydroxide was slowly added while keeping the temperature below 30C. Acronitrile (2.03 moles or 132.8 ml.) was added and the reactionallowed to proceed at room temperature, with occasional shaking, for 24hours. Nitrogen analysis of an aliquot taken from the reaction mixtureat this time indicated that one equivalent of acrylonitrile had reacted.The reaction mixture was then acidified with 4 moles (327.5 m1.) ofconcentrated hydrochloric acid whereupon crystals of mono-cyanoethylglutamic acid monohydrate began to form. The water was removed bydistillation at reduced pressure, leaving a sticky residue. Acetone (600ml.) was added to the residue and the mixture heated under reflux for 30minutes whereupon the cyanoethyl derivative went into solution. Sodiumchloride was then filtered off, washed with a small amount of acetone,and the washings were added to the filtrate. cooling to 30 C. with theaid of Dry Ice, 355 g. of crystals were obtained (yield of crude prodnot97 percent). Upon recrystallizing twice from Upon hot acetone, pureN-(2-cyanoethy1)-l-glutiminic acid was obtained:

Neutral equivalent: Calculated, 182.2;iound, 183. M. P.: 123.5-124 Cacetone 20.3

[0111), 0.1 M in 0.4 N HCl=7.3.

EXAMPLE 2 Mono-cyanoethyl-glutamic acid monohydrate was prepared byreacting acrylonitrile with disodium glutamate followed by acidifyingwith two equivalents of hydrochloric acid as described in Example 1. Thecrystals of mono-cyanoethyl-glutamic acid were filtered off, washed freeof chloride ions witlicold water, and air dried. N Anal: Found 12.75;Calcd. for the monohydrate 12.83. The water of crystallization could beremoved from this compound by drying over phosphorous pentoxide and bydrying in a vacuum oven for 3 hours at 100 C. This dried compound didnot give a true melting point. It was heated at 130 C. for 1.5 hours,and N-(2-cyanoethyl)-glutiminic acid was formed thereby (M. P. 122-124C.). This product may be isolated by taking it up with acetone, since itis soluble in acetone, whereas N-(Z-cyanoethyl) glutamic acid is not.

We claim:

1. N-(Z-cyanoethyl) -2-pyrrolidone-5-carboxylic acid of the followingformula:

2. The process which comprises heating monocyanoethyl-glutamic acid toeffect closure of the pyrrolidone ring and produce the compound of claim1.

3. The process which comprises reacting a salt of glutamic acid withacrylonitrile and reacting the product with a mineral acid, heating thereaction product to form the compound of claim 1.

4. The process which comprises reacting the disodium salt ofmonoecyanoethyl-glutamic acid with hydrochloric acid to formmono-cyanoethylglutamic acid monohydrate, removing water from thereaction mixture and heating the dried residue to formN-(2-cyanoethyl)-2-pyrrolidone-5- carboxylic acid and separating saidN-(Z-cyanoethyl) -Z-pyrrolidone-5-carboxylic acid from the reactionmixture.

LEONARD L. MCKINNEY. EUGENE H. UHING. JOHN C. COWAN.

No references cited.

1. N - (2 - CYANOETHYL) - 2 - PYRROLIDONE-5-CARBOXYLIC ACID OF THEFOLLOWING FORMULA: